Recent Publications by CFE Educators

Adult-onset leukoencephalopathy with spheroids and pigmented glia (ALSP) is an autosomal dominant leukoencephalopathy caused by mutations in colony stimulating factor 1 receptor (CSF1R). Here we report clinical and imaging outcomes following allogeneic haematopoietic stem cell transplantation (HSCT) in two patients with ALSP at the University of California, San Francisco between January 2016 and December 2017. Patient 1 proceeded to transplantation at age 53 with a haplo-identical sibling donor. Patient 2, whose sister and mother had died of the disease, proceeded to transplantation at age 49 with a 12/12 human leukocyte antigen-matched unrelated donor. Both patients received reduced intensity conditioning regimens. At 28 and 26 months post-HSCT, respectively, both patients were alive, without evidence of graft-versus-host disease, with major infection at 1 year in one and new-onset seizures in the other. In both cases, neurological worsening continued post-HSCT; however, the progression in cognitive deficits, overall functional status and gait impairment gradually stabilized. There was continued progression of parkinsonism in both patients. On brain MRI, within 1 year there was stabilization of T2/FLAIR abnormalities, and after 2 years there was complete resolution of abnormal multifocal reduced diffusion. In summary, after >2 years of follow-up, allogeneic HSCT in ALSP led to interval resolution of diffusion MRI abnormalities, stabilization of T2/FLAIR MRI abnormalities, and partial clinical stabilization, supportive of treatment response. Allogeneic HSCT may be beneficial in ALSP by providing a supply of bone marrow-derived brain-engrafting myeloid cells with donor wild-type CSF1R to repopulate the microglial niche.

OBJECTIVES

Epidemiological studies of underground miners have provided clear evidence that inhalation of radon decay products causes lung cancer. Moreover, these studies have served as a quantitative basis for estimation of radon-associated excess lung cancer risk. However, questions remain regarding the effects of exposure to the low levels of radon decay products typically encountered in contemporary occupational and environmental settings on the risk of lung cancer and other diseases, and on the modifiers of these associations. These issues are of central importance for estimation of risks associated with residential and occupational radon exposures.

METHODS

The Pooled Uranium Miner Analysis (PUMA) assembles information on cohorts of uranium miners in North America and Europe. Data available include individual annual estimates of exposure to radon decay products, demographic and employment history information on each worker and information on vital status, date of death and cause of death. Some, but not all, cohorts also have individual information on cigarette smoking, external gamma radiation exposure and non-radiological occupational exposures.

RESULTS

The PUMA study represents the largest study of uranium miners conducted to date, encompassing 124 507 miners, 4.51 million person-years at risk and 54 462 deaths, including 7825 deaths due to lung cancer. Planned research topics include analyses of associations between radon exposure and mortality due to lung cancer, cancers other than lung, non-malignant disease, modifiers of these associations and characterisation of overall relative mortality excesses and lifetime risks.

CONCLUSION

PUMA provides opportunities to evaluate new research questions and to conduct analyses to assess potential health risks associated with uranium mining that have greater statistical power than can be achieved with any single cohort.

Although only 1.3% of abortions in the United States are between 20 and 24 weeks' gestation, these procedures are associated with elevated risks of morbidity and mortality. Adequate cervical preparation before dilation and evacuation (D&E) at 20-24 weeks' gestation reduces procedural risk. For this gestational range, at least one day of cervical preparation with osmotic dilators is recommended before D&E. The use of overnight osmotic dilators alone is sufficient for most D&Es at 20-24 weeks' gestation. Dilapan-S® dilators require a shorter time to achieve maximum dilation, may be more effective than laminaria and may increase the likelihood of success on the first D&E attempt. The use of adjunctive mifepristone administered one-day pre-operatively at the time of osmotic dilator placement, should be considered because evidence demonstrates that it makes D&E subjectively easier at 20-24 weeks without increasing side effects. While older studies suggest that two-days of serial osmotic dilators provide greater dilation than one day of dilators, adjunctive mifepristone may be comparable to a second day of dilators. Adjunctive misoprostol administered on the day of D&E does not appear to affect initial cervical dilation and procedure time and compared with mifepristone is associated with more side effects, such as pain and nausea. Using overnight mifepristone and same-day misoprostol without osmotic dilators at 20-24 weeks' gestation lengthens D&E procedure time and appears to increase immediate complications, at least among less experienced providers. Some evidence shows the feasibility of same-day cervical preparation before D&E at 20-24 weeks using Dilapan-S® with adjunctive misoprostol or serial repeat dosing of misoprostol, but same-day preparation should be limited to providers with significant experience with these regimens. The Society of Family Planning recommends preoperative cervical preparation before D&E at 20-24 weeks' gestation. Further studies are needed to clarify the best means of preparing the cervix in order to minimize abortion complications and improve outcomes in this gestational range.

Non-syndromic orofacial clefts encompass a range of morphological changes affecting the oral cavity and the craniofacial skeleton, of which the genetic and epigenetic etiologic factors remain largely unknown. The objective of this study is to explore the contribution of underlying dentofacial deformities (also known as skeletal malocclusions) in the craniofacial morphology of non-syndromic cleft lip and palate patients (nsCLP). For that purpose, geometric morphometric analysis was performed using full skull cone beam computed tomography (CBCT) images of patients with nsCLP ( = 30), normocephalic controls ( = 60), as well as to sex- and ethnicity- matched patients with an equivalent dentofacial deformity ( = 30). Our outcome measures were shape differences among the groups quantified via principal component analysis and associated principal component loadings, as well as mean shape differences quantified via a Procrustes distance among groups. According to our results, despite the shape differences among all three groups, the nsCLP group shares many morphological similarities in the maxilla and mandible with the dentofacial deformity group. Therefore, the dentoskeletal phenotype in nsCLP could be the result of the cleft and the coexisting dentofacial deformity and not simply the impact of the cleft.